1) What timeframe are we confident that we will begin human clinical trials on hair cell regen?
The estimate that the panel professed was that it would be 25-50 years before we'll have something for humans. It was not clear if that was clinical trials, or a commercial product, or some other milestone. If they got $50 million in funding today, that would go a long way to being helping have something closer to 25 years. But all agreed it was at least "decades" away.
This $50 million, to put it into perspective:
a) is equal to only a tiny drop of the stimulus funds the US government is putting into the US economy;
b) with 30M deaf and hard of hearing Americans, if they all donated $1.50 or so today, that would equal $50M.
2) What trials are being done on animals or pre-human testing today?
Three animal tests were mentioned by the panelists - chicken/avian cochlea regerneration (started in 1986), mouse cochleas/vestibular systems, and guinea pig cochlea restoration via implanted matter. One panelist was working towards getting approval for an ape/monkey trial. Human trials are still quite a ways off Even once human trials are in effect, getting FDA approval could take 7-15 years.
3) How does one participate in such human clinical trials? What are the costs, requirements, and circumstances around such a trial?
This is a question that, frankly, isn't ready to be answered yet. Researchers are nowhere near enough to trial circumstances that any answers to this question can only be pulled out of thin air. In my opinion, there are quite a number of people who would throw their life savings, their bodies, and their lives at this chance to hear better. There will not be a shortage of people volunteering for trials like this when they're offered.
4) Assuming human trials are concluded and approved, what kind of hearing improvement could one reasonably expect from such a procedure? What hearing level, post-procedure, is realistic?
Again, this is a question that isn't ready to be answered yet. We don't even know what the actual solution is right now - to me, it sounded like 3 possible vectors were being analyzed:
1) Manipulation of the components of the affected ear to replace hair cell loss (via supporting cells) - this is a challenge because unlike chicken cochleas, the human cochlea is extremely complex and has a large number of interactions between components. Small changes can wildly disrupt the entire ear infrastructure, rending one unable to hear at all. We do not yet fully understand the interactions, more research needs to be done to map this.
2) Regeneration of hair cells via genetic science (cell mitosis) - studying the development of hair cells in mice, this may be possible via the introduction of medicine that causes cell regrowth. The issue is a) how much medicine; b) making sure the medicine gets to the right parts and c) making sure that the cell regrowth stops and does not become cancer.
3) Stem cell implantation. Mice and guinea pigs were subjected to noise damage then injected with stem cell matter to restore hearing. Results were that the matter injected found places where there was damage, but it's not clear if any hearing was restored. So it's not clear if any research being done in taking stem cells of ear parts and manipulating them into the cochlea directly is being successful . They did state that the idea of "transplanting" a functioning cochlea from a hearing person into a deaf person is probably impossible, again, because of the enormous complexity of the ear.
5) What kind of candidacy requirements are expected for such a procedure?
That isn't ready to be answered yet. It is expected that the first tests would be with people who lost their hearing to a specific kind of instance such as ototoxity (hearing loss from drugs). In nearly all noted research cases, the animal subject's hearing loss was caused by chemicals wiping out their hair cells.
6) How will one's existing hearing loss affect the expected improvement to one's hearing?
Unknown. A couple of things of note:
Diagnosis for the reason for hearing loss is the first step. If the hairs of the cochlea are not the only problem a patient faces, this specific therapy would not solve the hearing loss problem. Even though Math1 genes have been able to promote balance hair growth in mice, who knows if it'll have the same effect on human cochlea hairs?
An interesting article I've found post-symposium: http://www.audiologyonline.
The panel answered a question from the audience that they believe that having meningitis and ossification of the cochlea would render the nerves connected to the hair cells useless. Therefore, patients with that kind of problem would have no benefit from this treatment.
7) Will such improvements start in the low dBs, or to the highs, or across the board?
This was not mentioned in any of the discussions. All tests appeared to address across the board hearing loss, not any specific frequency field.
8) Is the procedure repeatable to continually improve one's hearing, or will it be a "one shot" deal?
Unknown.
9) What kind of costs are expected with this procedure? Will it be cheaper than getting a CI? Will it be affordable or only available to the rich?
Unknown, and far too early to tell.
10) What kind of insurance implications will take place with this procedure? Will it compare to what it is like today to get a CI?
Unknown.
11) What risks are expected for such a procedure?
One clear risk covered was that it is not yet known how to control the cell regeneration cycle. If too many hair cells are regenerating, then there is a risk that it will become a cancer.
12) Are there risks that may impact more than just the ear and hearing?
Cancer was one mentioned risk.
13) Is it expected to be safer than a CI, from both a surgery and lifestyle perspective?
Unknown. Too early to tell. One advantage to biological means of restoring hearing is that there would not be a need for providing battery power, for example, to CI equipment.
14) In such a procedure, would someone with some existing residual hearing run the risk of losing such residual hearing, i.e. go completely deaf if the procedure is not successful? Or will that hearing be left intact and the procedure simply supplement one's hearing loss?
In one instance, sound damage was used on mice and guinea pigs. Then neural stem cells were implanted into the animal's cochlea. A number of stem cells did survive and move to the correct location of cell damage. It was not clear from the presentation, however, whether this indicated the animal regained their hearing. Only that the stem cells did seem to do the "right thing."
15) Will having a CI already implanted complicate the procedure? Is it better to have "virgin ears" with residual hearing and no CI to remove?
This was not addressed at the presentation.
16) Would someone who has been deaf for a long time benefit from this procedure? Would it be better for someone to have a CI for a long time and have this procedure, or be deaf for a long time and have this procedure?
This was not addressed at the presentation.
17) Will CIs become obsolete shortly after this becomes available?
This was not addressed at the presentation.
18-NEW) Does it make a difference in the procedure's chances of success depending on whether the patient lost their hearing due to the environment, or due to their genes? I.e. what impact does this have on Connexin 26 patients?
The example of the ossification of the cochlea, where bone or other hard material make it impossible to connect cochlea hairs to nerves, does negate the benefits of hair cell regeneration. There must be other, similar circumstances, such as if no nerves are connected to the cochlea, or no way for the hair cells to regenerate in a cochlea. The nerves must be present and the cochlea able to transmit data to the nerves in order for hair cell regeneration to be effective.
You should post this on FB for all to read. It is great and could get someone to be motivated to get those unanswered questions addressed...also the link above about cord blood is very interesting, but seems to be for babies under 18 months who have had their hearing loss for a short time. Still seems a long way for the rest of us.
ReplyDelete